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Genetic variants underlying vitamin D metabolism and VDR-TGFβ-1-SMAD3 interaction may impact on HCV progression: a

Laura A de Azevedo1, Ursula Matte2,3, Themis R da Silveira1,3

  • 1Graduate Program in Gastroenterology and Hepatology Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Journal of Human Genetics
|July 14, 2017
PubMed

Insights

Genetic variants in vitamin D metabolism may influence chronic hepatitis C progression. A specific TGFB1 gene variant (rs1800469) was linked to hepatic decompensation in patients with hepatitis C.

Area of Science:

  • Genetics
  • Hepatology
  • Endocrinology

Background:

  • Vitamin D deficiency is common in liver disease.
  • Vitamin D may reduce hepatic fibrosis via anti-TGFβ-1/SMAD3 pathways.
  • Genetic variations in vitamin D pathways could affect chronic hepatitis C (HCV) progression.

Purpose of the Study:

  • To investigate the association between genetic variants in vitamin D metabolism and VDR/TGFβ-1/SMAD3 signaling with clinical outcomes in chronic HCV patients.
  • To identify specific single nucleotide polymorphisms (SNPs) that impact the progression of liver disease in individuals with chronic hepatitis C.

Main Methods:

  • Genotyped 40 single nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism and VDR/TGFβ-1/SMAD3 pathways.
  • Analyzed data from the HALT-C cohort, following 681 chronic HCV patients over 4 years.
  • Assessed associations between SNPs and outcomes like fibrosis worsening, hepatic decompensation, hepatocellular carcinoma, and liver death.

Main Results:

  • Eleven SNPs showed a tendency towards significance (P<0.05) for various outcomes.
  • SNPs in DHCR7, GC, CYP2R1, VDR, and SMAD3 were linked to different disease progressions.
  • A statistically significant association (P<0.00125) was found between the TGFB1 SNP rs1800469 and hepatic decompensation after Bonferroni correction.

Conclusions:

  • The TGFB1 gene variant rs1800469 is associated with hepatic decompensation in chronic hepatitis C.
  • Further evaluation in larger cohorts is needed for the 11 other identified polymorphisms to confirm the role of vitamin D in hepatitis C progression.

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